Stocksley Mark A, Chakkalakal Joe V, Bradford Amanda, Miura Pedro, De Repentigny Yves, Kothary Rashmi, Jasmin Bernard J
Department of Cellular and Molecular Medicine and Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ont., Canada K1H 8M5.
Neuromuscul Disord. 2005 Jun;15(6):437-49. doi: 10.1016/j.nmd.2005.03.008.
Upregulation of utrophin in muscle is currently being examined as a potential therapy for Duchenne muscular dystrophy patients. In this context, we generated transgenic mice harboring a 1.3 kb human utrophin A promoter fragment driving expression of the lacZ gene. Characterization of reporter expression during postnatal muscle development revealed that the levels and localization of beta-galactosidase parallel expression of utrophin A transcripts. Moreover, we noted that the utrophin A promoter is more active in slow soleus muscles. Additionally, expression of the reporter gene was regulated during muscle regeneration in a manner similar to utrophin A transcripts. Together, these results show that the utrophin A promoter-lacZ construct mirrors expression of utrophin A mRNAs indicating that this utrophin A promoter fragment confers temporal and spatial patterns of expression in skeletal muscle. This transgenic mouse will be valuable as an in vivo model for developing and testing molecules aimed at increasing utrophin A expression.
目前正在研究上调肌肉中肌养蛋白作为杜氏肌营养不良症患者的一种潜在治疗方法。在此背景下，我们构建了携带驱动lacZ基因表达的1.3 kb人肌养蛋白A启动子片段的转基因小鼠。对出生后肌肉发育过程中报告基因表达的表征显示，β-半乳糖苷酶的水平和定位与肌养蛋白A转录本的表达平行。此外，我们注意到肌养蛋白A启动子在慢肌比目鱼肌中更活跃。另外，报告基因的表达在肌肉再生过程中以类似于肌养蛋白A转录本的方式受到调控。总之，这些结果表明肌养蛋白A启动子-lacZ构建体反映了肌养蛋白A mRNA的表达，表明该肌养蛋白A启动子片段赋予了骨骼肌中表达的时空模式。这种转基因小鼠作为开发和测试旨在增加肌养蛋白A表达的分子的体内模型将具有重要价值。
